FDA vs. MDs: Who Calls Shots on Retin-A? : Medicine: Agency says doctors should wait for government approval before prescribing acne drug as a remedy for wrinkles.
The early reports tantalized: Retin-A, the highly successful acne cream, might help diminish some undesirable effects of sun-damaged skin--fine wrinkles, sagging, blotchiness.
After more than three years of hype and hoopla, however, the U.S. Food and Drug Administration has put the clamp on discussion of Retin-A as a treatment for sun-damaged skin, at least for now. Because it is officially approved only for acne, the FDA has charged that promotion of the drug for use as a wrinkle cream is premature and misleading.
The agency’s Retin-A warning has raised some broader medical and ethical questions as well:
* Under what circumstances should doctors prescribe a drug for a non-approved use?
* How do drug companies supply information to physicians about drugs under study without arousing public curiosity?
* Has the publicity surrounding Retin-A obscured the studies on whether it really works to diminish fine wrinkles and mottling?
The controversy began earlier this month, when FDA commissioner David Kessler announced that he would crack down on the marketing and promoting of prescription drugs for non-approved uses. Kessler specifically criticized Ortho Pharmaceutical, Retin-A’s manufacturer, for promoting the cream as a treatment for sun-damaged skin.
Last week, Kessler went one step further, warning doctors that to promote drugs for unapproved uses was to risk criminal prosecution. He also warned doctors against participating in events funded by drug companies that could be construed as promotional.
Although Kessler did not name Ortho, Retin-A or any doctors in last week’s bulletin, Ortho funded several now-controversial news conferences and educational seminars from 1986 to 1988 to discuss Retin-A’s potential as a wrinkle cream. Some dermatologists have admitted that Ortho sometimes paid them to speak at those forums.
How the FDA’s tightening of drug promotion and marketing will affect tens of thousands of consumers using Retin-A for wrinkles is unclear.
Physicians can legally prescribe a drug for any use. But the high-profile FDA-Ortho tussle has left some doctors hesitant to prescribe Retin-A for sun-damaged skin and has resurrected questions about its effectiveness.
“The marketing of Retin-A has been so strong that patients as well as dermatologists have been intoxicated,” says Dr. Patrick Abergel, a Santa Monica dermatologist. “Patients have come asking for the drug and doctors have tried to answer the demand of the public. Unfortunately, it is a drug with a number of side effects. And I’m not sure it is effective at all. I think it has been overemphasized as an anti-aging drug.”
In its criticism of Ortho, the FDA is reminding doctors and consumers that the cream has not been proven as a remedy for sun-damaged skin, says Dr. David Fulghum, a Bradenton, Fla., dermatologist who has researched Retin-A and wrinkles and is an American Academy of Dermatology spokesman.
“I think some of the doctors will be less enthusiastic in prescribing it now,” he says.
But Dr. Gerald Weinstein, chairman of dermatology at UC Irvine and one of the scientists investigating Retin-A for use in helping sun-damaged skin, disagrees:
“I don’t think the FDA is saying that at all (that it doesn’t work). I think they are saying that there is a way to bring the drug out on the market.”
Weinstein says the FDA’s complaint is specifically with the manufacturer’s marketing practices and should not affect physicians.
Some doctors are concerned, however, that the agency could, in its zeal to curb inappropriate marketing, interfere in their right to obtain important scientific information from a drug manufacturer and, correspondingly, help patients as they see fit.
Unusually high consumer interest in the drug complicates the picture, experts say. Although dozens of cosmetic companies make creams and moisturizers to improve skin tone, Retin-A is the only drug (as opposed to a cosmetic) that some studies have shown to have therapeutic value.
Retin-A is the brand name for retinoic acid or tretinoin, a Vitamin-A derivative first approved for acne use in 1971. Acne patients, however, soon reported that the cream made their skin smoother and rosier, and studies were launched in 1987 on the drug’s effects on sun-damaged skin.
In January, 1988, an article in the Journal of the American Medical Assn. reported improvement in sun-damaged skin from Retin-A. The announcement of favorable preliminary studies caused sales of the cream to soar from $33.5 million in 1987 to $115 million in 1988, according to Money magazine.
(Ortho would not release its sales figures for any year. But prices of Retin-A have soared as well. A 20-gram tube that sold for about $25 two years now costs about $50.)
In December, 1989, a six-month double-blind study of 650 patients--the largest study of the drug--showed that 68% of people using the cream experienced reductions in fine wrinkles and pigmentation. In a group using a placebo, 38% showed improvement, says Weinstein.
Other studies also suggest that the cream diminishes the scaly precancerous lesions called actinic keratoses.
“I have seen absolutely no major problems whatsoever, and I think it’s an outstanding agent to help actinically damaged (sun-damaged) skin,” says Dr. David Morrow, a dermatologic plastic surgeon and director of Morrow Skin Institute in Rancho Mirage. “One has to ask why the FDA is doing this. I think if the FDA is going to endeavor to have a policy that doctors can only use this for acne, we’re going to have problems. Doctors won’t comply en masse.”
Consumers want Retin-A for wrinkles, Morrow says: “Patients say, ‘Here goes the government putting their nose into something they shouldn’t be.’ People want to deal with their doctors directly.”
The FDA has requested a federal investigation to determine whether Ortho violated FDA drug promotion rules. Ortho spokesman Rich Salem says the company is cooperating with that investigation.
Salem says the company, a subsidiary of Johnson & Johnson, has tried to meet demands for information about the product without promoting its use as a wrinkle cream. A 1988 news conference on Retin-A’s effects on wrinkles, which was coordinated with the publication of a major study, is at the heart of the government’s investigation. But Salem says the event was organized and directed by a researcher involved in the study. Ortho, however, did pay for the conference at the researcher’s request, Salem says.
“We do feel that our dissemination of information about our photo-damaged, or sun-damaged, skin studies was proper and that balanced and medically accurate information was made available to all communities interested in this,” including medical professionals and the public, he says.
Salem says Ortho has submitted a new FDA application to gain approval for use of the drug for sun-damaged skin, which would allow the company to promote and market the cream for that purpose. The new product is a different formulation than the acne cream and would be sold under the trade name Renova. The agency has not yet ruled on that application.
Meanwhile, debate continues whether the substance works and how it works.
A study in the Journal of the American Medical Assn. in January, 1990, suggested that Retin-A works in part by augmenting the number of tissue fibers that help bind the skin’s outer layer, the dermis, to the inner layer. Wrinkling occurs when the underlying dermis loses its elasticity and shrinks, causing the skin’s outer layer to sag and fold. Studies have also suggested that the cream thickens the outer layer and increases blood flow to the skin.
But, according to Fulghum, other studies have suggested that Retin-A merely irritates the skin, causing the dead surface cells to slough off. Other skin irritants would work just as well, he says.
Studies continue to look at effects of Retin-A in various strengths and on patients with varying degrees of sun-damaged skin, Weinstein says. He says, however, that earlier studies have concluded that the substance imparts modest improvements to many users and can, in a smaller number of cases, lead to more dramatic improvements. The effects are most beneficial when patients also avoid long exposure to the sun, wear a strong sunscreen and use a moisturizing cream daily.
Retin-A is not without side effects. The cream can cause redness, itching, peeling, scaliness and dryness. It can also irritate the skin around the eyes. Most important, the drug increases the skin’s sensitivity to sunlight. Retin-A users need to avoid the sun or wear a highly protective sunscreen to avoid severe sunburn.
The hype surrounding Retin-A has masked many of the warnings about side effects, says dermatologist Abergel. This might be a factor in the FDA’s desire to crack down on premature marketing.
“We’ve heard too many good things and not enough of the true story,” he says of the lack of publicity given to skin irritation and sunburn associated with the drug. “We are seeing a lot of side effects of Retin-A that the public is not too well-informed about.”
